title: Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California: results of the first 2 years.
abstract: BACKGROUND
  Assay of T-cell receptor excision circles (TRECs) in dried blood spots obtained at birth permits population-based newborn screening (NBS) for severe combined immunodeficiency (SCID).
  
  
  OBJECTIVE
  We sought to report the first 2 years of TREC NBS in California.
  
  
  METHODS
  Since August 2010, California has conducted SCID NBS. A high-throughput TREC quantitative PCR assay with DNA isolated from routine dried blood spots was developed. Samples with initial low TREC numbers had repeat DNA isolation with quantitative PCR for TRECs and a genomic control, and immunophenotyping was performed within the screening program for infants with incomplete or abnormal results. Outcomes were tracked.
  
  
  RESULTS
  Of 993,724 infants screened, 50 (1/19,900 [0.005%]) had significant T-cell lymphopenia. Fifteen (1/66,250) required hematopoietic cell or thymus transplantation or gene therapy; these infants had typical SCID (n = 11), leaky SCID or Omenn syndrome (n = 3), or complete DiGeorge syndrome (n = 1). Survival to date in this group is 93%. Other T-cell lymphopenic infants had variant SCID or combined immunodeficiency (n = 6), genetic syndromes associated with T-cell impairment (n = 12), secondary T-cell lymphopenia (n = 9), or preterm birth (n = 8). All T-cell lymphopenic infants avoided live vaccines and received appropriate interventions to prevent infections. TREC test specificity was excellent: only 0.08% of infants required a second test, and 0.016% required lymphocyte phenotyping by using flow cytometry.
  
  
  CONCLUSIONS
  TREC NBS in California has achieved early diagnosis of SCID and other conditions with T-cell lymphopenia, facilitating management and optimizing outcomes. Furthermore, NBS has revealed the incidence, causes, and follow-up of T-cell lymphopenia in a large diverse population.
authors.affiliation: Department of Pediatrics, University of California San Francisco and UCSF Benioff Children's Hospital, San Francisco, CA 94143-0519, USA.
authors.forename: Antonia
authors.initials: A
authors.lastname: Kwan
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Church
authors.forename: Morton J
authors.initials: MJ
authors.lastname: Cowan
authors.forename: Rajni
authors.initials: R
authors.lastname: Agarwal
authors.forename: Neena
authors.initials: N
authors.lastname: Kapoor
authors.forename: Donald B
authors.initials: DB
authors.lastname: Kohn
authors.forename: David B
authors.initials: DB
authors.lastname: Lewis
authors.forename: Sean A
authors.initials: SA
authors.lastname: McGhee
authors.forename: Theodore B
authors.initials: TB
authors.lastname: Moore
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stiehm
authors.forename: Matthew
authors.initials: M
authors.lastname: Porteus
authors.forename: Constantino P
authors.initials: CP
authors.lastname: Aznar
authors.forename: Robert
authors.initials: R
authors.lastname: Currier
authors.forename: Fred
authors.initials: F
authors.lastname: Lorey
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Puck
mesh_terms: D002140:California; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008231:Lymphopenia / Q000175:diagnosis*; D008297:Male; D015997:Neonatal Screening; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis*; D013601:T-Lymphocytes / Q000276:immunology*